This application requests five years of continued support for a multi- disciplinary, biological, and psychological program of research of Mental Retardation and Developmental Psychopathology. The Program emphasizes the interaction of neuro-maturational, genetic, and environmental factors in the emergence and natural course of individuals with mental retardation and developmental disorders. The program is unified by a shared theoretical perspective, methods, and research strategies. Studies concern processes leading to adaptation and areas of competence, as well as to specific disabilities and dual diagnosis (mental retardation + psychopathology) in well-defined syndromes. Treatment studies are proposed that relate to basic, underlying mechanisms. The four Research Project Areas focus on major domains of theoretical and clinical importance in relation to the understanding and amelioration of mental retardation and developmental disorders: 1) the development of children exposed to drugs in utero and growing up in high-risk environments: 2) Tourette's syndrome and associated disorders as models for understanding gene-environment interaction in developmental disorders; 3) neuropsychological and neurobiological differentiation of autism and Asperger's syndrome; and 4) familial and genetic influences on the developmental trajectories of individuals with specific syndromes of mental retardation. The program is supported by three Core Research Resources: Administration; Assessment; and Biostatistics and Methodology. These Cores provide state-of-the art collaboration and consultation.